Model gives insight into HIV vaccines

Researchers in China have created what they claim is the most "detailed and realistic" model of HIV to date, and say that it could help in the creation of a vaccine for the deadly virus. However, immunologists warn that the model is yet to catch up with modern clinical trials.

According to the World Health Organization, HIV is one of the world's biggest health challenges, infecting almost three million people and killing some two million people every year. When a person is infected, HIV enters into the immune system's crucial T lymphocytes – or T cells – and replicates itself by integrating with the DNA. As a result the cells die and the immune system slowly weakens until it can no longer fight off opportunistic infections, a status classified as AIDS.

The scale of the AIDS epidemic has prompted many scientists to search for an HIV vaccine, but this has proved difficult. HIV is different from other viruses in that it can mutate very quickly, thereby evading the normal immune-system defences. Some scientists think that a vaccine will only become available once there is a leap in the theoretical understanding of the virus.

'Detailed and realistic'

Physicist Jianwei Shuai and chemical biologist Hai Lin of Xiamen University now think they have a model that will help with that understanding. "We propose a more detailed and realistic HIV model than previous models, by incorporating many important features of HIV dynamics," says Shuai.

In the model, single HIV particles, known as virions, sit on lattice sites alongside two types of T cell: CD4+ T cells, which direct other immune-system cells, and CD8+ T cells, which kill infected cells. The virions and cells take a "random walk" around the lattice sites until two meet each other, at which point they interact in one of several ways. At the same time, the model takes into account the virions' mutations and the responses of the T cells.

One of the results of the researchers' model concerns the so-called asymptomatic phase in HIV-positive patients – the period from which they are infected with HIV to when they begin to develop AIDS. Although for the majority of people this phase is 5–10 years, it can be 15 years or longer. Physicians had thought the discrepancy was due to the abilities of different patients' immune systems, but Shuai and Lin think the reason could simply be a product of the immune system's random response.

Decisive role

A potentially more important result, however, comes in the way that the two types of T cell react to HIV. In their model, Shuai and Lin found that it is the CD8+ T cells that play a decisive role in suppressing the virus. "This observation implies that CD8+ T-cell response might be an important goal in the development of an effective vaccine against AIDS," explains Shuai.

Yet some researchers claim that this result is nothing new. "The model makes a large number of assumptions, none of which are examined by comparison to [clinical] data," says Alan Perelson, a theoretical immunologist at Los Alamos National Laboratory, US. "That CD8+ T cells might be important in suppressing viral load is not novel, and in fact was the basis of the large trial that failed to provide protection."

Mathematical exercise?

David Ho, an AIDS scientist at the Aaron Diamond Research Center in New York, is also critical of the results. "Playing with math to fit clinical data is just an exercise," he says.

Still, Shuai and Lin are planning to take their model further. By modelling the effects of different drugs, they hope to find an optimal therapy to fight HIV.